A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE) in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis

Richard N Greenberg, Maria Yadira Hurley, Dinh V Dinh, Serena Mraz, Javier Gomez Vera, Dorothea von Bredow, Alfred von Krempelhuber, Siegfried Roesch, Garth Virgin, Nathaly Arndtz-Wiedemann, Thomas Peter Meyer, Darja Schmidt, Richard Nichols, Philip Young, Paul Chaplin, Richard N Greenberg, Maria Yadira Hurley, Dinh V Dinh, Serena Mraz, Javier Gomez Vera, Dorothea von Bredow, Alfred von Krempelhuber, Siegfried Roesch, Garth Virgin, Nathaly Arndtz-Wiedemann, Thomas Peter Meyer, Darja Schmidt, Richard Nichols, Philip Young, Paul Chaplin

Abstract

Background: Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD). Prior studies evaluating Modified Vaccinia Ankara virus (MVA), a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.

Objective: This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30) and 282 healthy subjects.

Methods: Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.

Results: The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.

Limitations: The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.

Conclusion: MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.

Trial registration: ClinicalTrials.gov NCT00316602.

Conflict of interest statement

Competing Interests: This study was funded by Bavarian Nordic through NIAID contract #N01-AI-40072. Rx Clinical Research, Inc. received grants from Bavarian Nordic. DVD is employed by Rx Clinical Research, Inc.. DB, AK, RS, GV, NA, TM, DS, RN, PY and PC were employed by Bavarian Nordic at the time of this study. The current employment is found on the title page of the submission. PC is holding patents in relation to MVA-BN (Modified Vaccina Ankara Virus Variant, International Publication Number WO 02/42480 A2). Additional MVA-BN patents based on this patent and other MVA patents are listed in a Supporting Information file. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Disposition of subjects.
Fig 1. Disposition of subjects.
AD = atopic dermatitis; n = number of subjects in the specified category; FAS = full analysis set; PPS = per-protocol analysis set. a: There was one subject that did not receive the second vaccination but did not terminate the study prematurely, i.e. returned for the final visit. b: more than one reason per subject possible. c: 10 subjects with currently active AD had a SCORAD >30 at screening; 2 of these subjects had a SCORAD >39 and were excluded from PPS as major protocol violations. For the volunteers that were excluded from the PPS but had samples available, immunogenicity results were similar to those of the PPS subjects.
Fig 2. Seroconversion.
Fig 2. Seroconversion.
Seroconversion rates were determined by vaccinia-specific ELISA (A) and PRNT (B). Data set is FAS (full analysis set), N = 632 (for Week 32 N = 235). Error bars represent upper and lower confidence intervals. Vaccinations were given at Week 0 and Week 4. AD = atopic dermatitis.
Fig 3. Antibody Titers.
Fig 3. Antibody Titers.
Geometric mean titers determined by vaccinia-specific ELISA (A) or PRNT (B). Data set is FAS (full analysis set), N = 632 (for Week 32 N = 235). Error bars represent upper and lower confidence intervals. Vaccinations were given at Week 0 and Week 4. AD = atopic dermatitis.

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